BERNARDO HOUSSAY CONFERENCE: Topics of immunity and diabetes mellitus reviewed in the light of basic science and current technologies

Abstract

Conventional methods for measuring autoantibodies, called markers, in diabetes mellitus with an autoimmune component (type 1 diabetes and LADA), have been radiometric or enzymatic (ELISA). Anti-insulin autoantibodies (IAA) were among the first to be studied. Antibodies with the same specificity have also been detected in diabetic patients treated with insulin (AI) and in other rare diseases. In all these cases, the aforementioned tests were shown to be very sensitive, but they had the limitation of expressing relative results because they could not distinguish the two constituent parameters of the analytical signals, such as affinities and concentrations. The so-called absolute methods can discriminate these parameters and are appropriate to study in depth the cases in which very high levels of IAA or IA appear through conventional preliminary analyses.

We have selected three work models requested from our laboratory at the Institute of Humoral Immunity Studies (IDEHU, CONICET-UBA), required from different medical groups or by the biotechnology pharmaceutical industry. The common problem of these special studies was to overcome the limitations of the usual methods for measuring high-level specific anti-insulin antibodies and move to a higher level of complexity that would allow defining the real absolute levels of these antibodies. The objectives of the works published in these lines were diverse, such as providing more precise diagnostic support, or reorienting therapeutic administration in favor of insulin analogues. For the latter, the concepts of cross-reactivity and specificity in immunology were also reviewed in order to introduce the selectivity parameter (S), which allows the most precise quantitative expression of the interaction of antibodies against a panel of antigens with structural homologies. Finally, contributions were made to quality control required by official regulatory authorities for recombinant insulins produced by the biotechnology industry.  

For all these approaches, the theoretical and practical scientific bases of radiometry were presented, which historically allowed the weighting of antibodies based on their absolute parameters, and the principles of current biosensors were incorporated, based on surface plasmonic resonance, which includes the determination of the kinetic parameters.